The nonobese diabetic (NOD) mouse is an excellent model of insulin-dependent (type I) human diabetes mellitus. We report that a single injection of complete Freund's adjuvant (CFA) given at an early age (5 wk) prevented the appearance of diabetes and greatly increased the life span of NOD mice without additional therapy. No treated mouse developed hyperglycemia by the age of 12 mo (n = 13), whereas all untreated mice died of diabetes before 8 mo of age (n = 38). All CFA-treated mice were alive and healthy at 12 mo of age. Some CFA-treated NOD mice that were monitored for long-term survival are still alive with no sign of disease at 18 mo of age (n = 5). Administration of CFA resulted in decreased in vitro splenic lymphocyte proliferative responses to alloantigen and mitogen. Cell-mixing experiments indicated that antigen-nonspecific inhibitory cells were elicited in the spleen and increased in the bone marrow. These regulatory cells were Thy-1− ; and nonadherent to nylon wool, as has been described for natural suppressor (NS) cells. These data lend support to a relationship between the boosting of endogenous NS activity and the establishment of tolerance to self in the context of autoimmunity. Our results suggest that early nonspecific immunotherapy of genetically predisposed individuals could prevent the development of autoimmune diabetes.
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Original Articles| May 01 1990
Prevention of Type I Diabetes in NOD Mice by Adjuvant Immunotherapy
Michel W J Sadelain;
Address correspondence and reprint requests to Dr. Bhagirath Singh, Department of Immunology, 8-60 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
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Michel W J Sadelain, Hui-Yu Qin, Jana Lauzon, Bhagirath Singh; Prevention of Type I Diabetes in NOD Mice by Adjuvant Immunotherapy. Diabetes 1 May 1990; 39 (5): 583–589. https://doi.org/10.2337/diab.39.5.583
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